This Research Scientist Award Application continues a line of research aimed at gaining a better understanding of the role of the parent-infant relationship in development. The proposed experiments focus on the acute isolation response of infant rats and its expression, the separation cry. This behavior provides a promising model for studying the development of anxiety. There is good evidence that During the last grant period, Dr. Hofer and colleagues discovered a novel maternal separation effect in which brief passive contact or certain active interactions of an isolated pup with its dam doubles or triples its subsequent rate of ultrasonic vocalization (USV). This maternal potentiation of the isolation response reveals the existence of a hitherto unsuspected system of affective communication between the rat mother and her pups. The proposed studies will explore the central neuromodulator pathways mediating maternal potentiation, the behavioral processes that control it, and the course of its postnatal development. In doing so, the investigator will test a novel hypothesis for its adaptive role, based on the potential evolutionary costs and benefits of high and low USV response to isolation. He and his colleagues will study the microevolution of differences in this trait as they emerge in the selectively bred lines, and will then exploit these differences, using neuropharmacologic techniques to reveal the central neural pathways primarily involved. Finally, they will explore the developmental continuity that may exist between this infantile trait and later affective responses in weanlings, juveniles and adults.